This application is for partial funding of the fourth and fifth FASEB Summer Research Conferences on "Nuclear Structure and Cancer" that will be held June 16-21, 2007 and in 2009, at the Vermont Academy in Saxtons River, Vermont. The conferences are under the auspices of the Federation of American Societies for Experimental Biology (FASEB). For both conferences, there will be 9 platform sessions, a workshop on molecular imaging in living cells and animal models and two poster sessions. Young investigators will be encouraged to give short talks at the regular platform and workshop sessions by selection from the submitted abstracts. The meetings will bring together basic and clinical investigators from academia and the private sector to focus on understanding the role of altered nuclear structure in the cancer process. These conferences will provide forums to evaluate the fundamental regulatory and clinical implications of modified temporal and spatial organization of nucleic acids and regulatory proteins that control gene replication, repair and expression in nuclei of tumor cells. The study of tumor-related changes in nuclear morphology and the subnuclear organization, nuclear import, intranuclear trafficking and assembly of regulatory factors is becoming increasingly relevant from both basic biological and clinical perspectives. There is a need for this conference that is dedicated to examining the structural and functional properties of the interphase nucleus in cells that are structurally and functionally compromised with the onset and progression of cancer. Mechanisms that interrelate nuclear morphology with gene replication, repair and expression will be systematically explored. There will be a concerted effort to critically evaluate emerging findings that interface nuclear organization with the assembly of regulatory machinery that governs the combinatorial control of genomic function. Epigenetic regulatory mechanisms will be addressed. Consideration will be given to contributions from cellular, biochemical, in vivo genetic and molecular approaches and their integration into multidisciplinary strategies for understanding the interrelationships among genomic organization, function, and cancer. Relevance: The objective of these meetings will be to develop experimental agendas that incorporate novel concepts and high resolution state-of-the-art methodologies for defining perturbations in nuclear architecture that are related to changes in the regulation of gene replication, repair, and expression in cancer cells. It is realistic to anticipate insight into components of nuclear organization that can be selectively targeted for innovative cancer diagnosis and therapy.